Meet Alex—Before and After NIH Clinical Trial
Posted on by Dr. Francis Collins
Alex Barton recently turned 17. That’s incredible because Alex was born with a rare, often fatal genetic disease and wasn’t expected to reach his teenage years.
When Alex was born, he looked like he’d been dipped in boiling water: his skin was bright red and blistered. He spent most of his time sleeping. When awake, he screamed in agony from headaches, joint pain, and rashes. After a torturous 14 months, a rheumatologist told his mother that Alex suffered from Neonatal-Onset Multisystem Inflammatory Disease (NOMID). The doctor showed her a brief and scary paragraph in a medical text. Kate Barton, Alex’s mother, admitted that it “knocked her over like a freight train.”
NOMID is the most severe form of an autoinflammatory disease spectrum called Cryopyrin-Associated Periodic Syndromes (CAPS). In 2001, researchers discovered the cause: a genetic mutation in a gene called NLRP3, which makes a protein called cryopyrin. Cryopyrin is part of a sensor in white blood cells that detects bacteria, harmful chemicals, and proteins produced by stressed, damaged, or dying cells. When the sensor detects these danger molecules, it launches an inflammatory response by activating a potent inflammatory protein called interleukin-1β.
In children with NOMID, the mutation yields an overactive sensor that triggers constant release of IL-1β and thus inflammation. This causes fever, rashes, meningitis, joint pain, and unregulated bone growth. If untreated, inflammation in the ear causes hearing loss, and inflammation in the brain can lead to blindness and mental retardation.
When Alex came to the NIH in 2003 at age six to participate in a clinical trial, he was covered in a head to toe rash, had partial hearing loss, vision problems, and couldn’t walk.
Dr. Raphaela Goldbach-Mansky, a rheumatologist at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, launched a clinical trial together with other NIH specialists to test a drug called anakinra (Kineret®), which the FDA had approved for rheumatoid arthritis (RA). Anakinra hadn’t been very effective for RA, but Goldbach-Mansky knew its mechanism should allow it to block cells from responding to IL-1β, curbing the inflammation that was destroying Alex’s body.
Just a few hours after Alex got his first injections of anakinra, the rash disappeared. Six days later, Alex was back on his feet and walking out of the NIH Clinical Center, where he recently came back to visit for his 10-year checkup. Goldbach-Mansky says that the results are truly astonishing. Of the estimated 80 or so children with NOMID in the United States, 53 are in her clinical trial on the NIH campus. Many of these patients were in such severe pain that they needed daily pain medication to sleep. After just a couple days of anakinra injections, these children were pain-free [1, 2].
Based on Goldbach-Mansky’s trial data, the FDA approved the use of anakinra for NOMID. You may be surprised to know that anakinra and other related drugs are now also being tested for conditions like gout, type 2 diabetes, and heart disease—diseases that also involve inflammation and that together affect tens of millions of people nationwide. If IL-1β triggers inflammation in these diseases, as it does in NOMID, then anakinra and other IL-1β blockers might prove to be an effective treatment.
So what’s the outlook for Alex? Goldbach-Mansky says that it’s difficult to say whether anakinra will always be effective for treating Alex’s condition. But it has been 10 years so far, and Alex has big plans for the coming year. He’s an excellent student and a fine musician and plans to go to college to study cello or medicine. I say, why not both?
References and links to more information:
 Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes. Sibley CH, Plass N, Snow J, Wiggs EA, Brewer CC, King KA, Zalewski C, Kim HJ, Bishop R, Hill S, Paul SM, Kicker P, Phillips Z, Dolan JG, Widemann B, Jayaprakash N, Pucino F, Stone DL, Chapelle D, Snyder C, Butman JA, Wesley R, Goldbach-Mansky R. Arthritis Rheum. 2012 Jul;64(7):2375-86.
 Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, Kim HJ, Brewer C, Zalewski C, Wiggs E, Hill S, Turner ML, Karp BI, Aksentijevich I, Pucino F, Penzak SR, Haverkamp MH, Stein L, Adams BS, Moore TL, Fuhlbrigge RC, Shaham B, Jarvis JN, O’Neil K, Vehe RK, Beitz LO, Gardner G, Hannan WP, Warren RW, Horn W, Cole JL, Paul SM, Hawkins PN, Pham TH, Snyder C, Wesley RA, Hoffmann SC, Holland SM, Butman JA, Kastner DL. N Engl J Med. Aug 10;355(6):581-92.
NIH Study Contributes to Approval of Promising Treatment for Genetic Inflammatory Disorder
Anakinra Clinical Trial for NOMID patients
NIH support: National Institute of Arthritis and Musculoskeletal and Skin Diseases; NIH Intramural Research Programs (National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Cancer Institute, National Institute on Deafness and Other Communication Disorders; National Eye Institute; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; Clinical Center)
Alex looks wonderful. He should just go from strength to strength.
I will never forget when I was trying to find out what was wrong with my grandson, you helped me so much by highlighting what symptoms we should look out for. Thank you. I am so glad Alex is thriving, our grandson is too.
Enjoy every sec of your life, Alex. I’m sure you can be strong.
Alex you are blessed to be cared by the staff at NIH.
Congratulations, Alex, and GO TEXANS!
For those Blog readers who might be wondering about your “Go Texans!” remark, Alex and his family happen to live in Texas. To take part in this clinical trial, they came to the NIH Clinical Center, which is located in Bethesda, M.D., just outside of Washington, D.C.
To learn more about clinical trials being carried out at the NIH Clinical Center and many other locations all across the United States and around the world, go to http://www.clinicaltrials.gov
Oh! His skin was bright red and blistered, and now Alex looks like a handsome guy. Enjoy life, every time 🙂
You are a brilliant star! Thank you for sharing your inspirational story. Wishing you health and happiness.
The Bowen Family
Alex has always been a star and an inspiration, so well done you! Had the pleasure to meet you and wishing you the very best, mate